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Association of metformin, sulfonylurea and insulin use with brain structure and function and risk of dementia and Alzheimer's disease: Pooled analysis from 5 cohorts.

TitleAssociation of metformin, sulfonylurea and insulin use with brain structure and function and risk of dementia and Alzheimer's disease: Pooled analysis from 5 cohorts.
Publication TypeJournal Article
Year of Publication2019
AuthorsWeinstein G, Davis-Plourde KL, Conner S, Himali JJ, Beiser AS, Lee A, Rawlings AM, Sedaghat S, Ding J, Moshier E, van Duijn CM, Beeri MS, Selvin E, M Ikram A, Launer LJ, Haan MN
Secondary AuthorsSeshadri S
JournalPLoS One
Volume14
Issue2
Paginatione0212293
Date Published2019
ISSN1932-6203
KeywordsAlzheimer Disease, Brain, Cognition, Cohort Studies, Dementia, Humans, Hypoglycemic Agents, Incidence, Insulin, Linear Models, Magnetic Resonance Imaging, Metformin, Proportional Hazards Models, Risk Factors, Sulfonylurea Compounds
Abstract

OBJECTIVE: To determine whether classes of diabetes medications are associated with cognitive health and dementia risk, above and beyond their glycemic control properties.

RESEARCH DESIGN AND METHODS: Findings were pooled from 5 population-based cohorts: the Framingham Heart Study, the Rotterdam Study, the Atherosclerosis Risk in Communities (ARIC) Study, the Aging Gene-Environment Susceptibility-Reykjavik Study (AGES) and the Sacramento Area Latino Study on Aging (SALSA). Differences between users and non-users of insulin, metformin and sulfonylurea were assessed in each cohort for cognitive and brain MRI measures using linear regression models, and cognitive decline and dementia/AD risk using mixed effect models and Cox regression analyses, respectively. Findings were then pooled using meta-analytic techniques, including 3,590 individuals with diabetes for the prospective analysis.

RESULTS: After adjusting for potential confounders including indices of glycemic control, insulin use was associated with increased risk of new-onset dementia (pooled HR (95% CI) = 1.58 (1.18, 2.12);p = 0.002) and with a greater decline in global cognitive function (β = -0.014±0.007;p = 0.045). The associations with incident dementia remained similar after further adjustment for renal function and excluding persons with diabetes whose treatment was life-style change only. Insulin use was not related to cognitive function nor to brain MRI measures. No significant associations were found between metformin or sulfonylurea use and outcomes of brain function and structure. There was no evidence of significant between-study heterogeneity.

CONCLUSIONS: Despite its advantages in controlling glycemic dysregulation and preventing complications, insulin treatment may be associated with increased adverse cognitive outcomes possibly due to a greater risk of hypoglycemia.

DOI10.1371/journal.pone.0212293
Alternate JournalPLoS One
PubMed ID30768625
PubMed Central IDPMC6377188
Grant ListUH3 NS100605 / NS / NINDS NIH HHS / United States
R01 AG054076 / AG / NIA NIH HHS / United States
RF1 AG059421 / AG / NIA NIH HHS / United States
U01 HL096917 / HL / NHLBI NIH HHS / United States
HHSN268201500001I / HL / NHLBI NIH HHS / United States
K24 DK106414 / DK / NIDDK NIH HHS / United States
U01 HL096814 / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
R01 AG034087 / AG / NIA NIH HHS / United States
U01 HL096812 / HL / NHLBI NIH HHS / United States
R01 NS017950 / NS / NINDS NIH HHS / United States
T32 HL007024 / HL / NHLBI NIH HHS / United States
N01 AG012100 / AG / NIA NIH HHS / United States
R01 DK089174 / DK / NIDDK NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
U01 HL096902 / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
R01 HL070825 / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
N01 HC025195 / HC / NHLBI NIH HHS / United States
R01 AG051545 / AG / NIA NIH HHS / United States
U01 AG052409 / AG / NIA NIH HHS / United States
U01 HL096899 / HL / NHLBI NIH HHS / United States
P30 AG010129 / AG / NIA NIH HHS / United States